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Background: Delayed gastric emptying (DGE) is a common cause of morbidity after pancreaticoduodenectomy (PD). DGE can be a source of distress and discomfort to patients, resulting in prolonged hospital stays and subsequent drain on staff and resources. AIMS: We aimed to investigate whether any preoperative or intraoperative variables predict risk of DGE. Ability to predict DGE would potentially enable therapeutic interventions such as insertion of a feeding jejunostomy at the time of PD in high-risk patients. METHODS: We performed a retrospective chart review of 523 patients who underwent PD at our institution between 2000 and 2009; 384 resections were performed since 2005. Data collected included: patient demographics, preoperative symptoms, preoperative chemoradiotherapy, type of resection performed (pylorus-preserving PD or standard PD, with or without vascular resection) OR time, estimated blood loss and transfusions, tumor size and histology, lymph node status, postoperative hematocrit and leukocyte count and postoperative NSAID use. We defined DGE as failure to tolerate a regular diet by postoperative day seven. Data was analyzed with alpha=0.05 using Fisher exact test for categorical variables and Mann-Whitney U test for continuous variables. RESULTS: A total of 114 patients with DGE were compared with 134 patients without DGE. Patients who suffered DGE were significantly more likely to have smaller tumors (p=0.015) and fewer positive lymph nodes (p=0.025), while patients without DGE were more likely to have received preoperative chemotherapy (p= 0.005) or preoperative radiation (p= 0.010). A possible explanation for these results is that patients with malignant disease have less normal functioning pancreatic parenchyma and are consequently less at risk for digestive symptoms resulting from pancreatic injury and inflammation. In addition, DGE was associated with an infection during hospitalization (p=0.008.) Hematocrit on the third postoperative day was significantly lower (p=0.019) for patients who experienced DGE , excluding patients who experienced post-operative bleeding. We hypothesize that DGE patients experienced more postoperative third space sequestration and bowel edema, resulting in greater hemodilution when sequestered fluid redistributed back into the vasculature. CONCLUSIONS: Contrary to our expectations, patients with smaller tumors and benign disease were more likely to experience DGE than patients with more advanced, malignant disease. As our ability to diagnose premalignant lesions improves, there will likely be more PD performed for benign disease, with a subsequent increase in the frequency of patients with DGE.